Considerable variation has been reported for placental-type alkaline phosphatase in cancer patients and in placentae, which, in the latter case, is allelic. In this study, immunochemical reagents have been developed to identify variant-specific structural determinant, using both rabbit antisera and monoclonal antibodies. Using these reagents, the association of specific variants with gynecological cancer fluids and tumor tissues, as well as xenograft specimens from cultured cell lines and from ovarian cancer patients in nude mice, is being investigated. At present, the results indicate that there are probably two genes coding for human placental-type alkaline phosphatase, that which codes for the enzyme found in the human placenta and that which codes for a distinct enzyme with different immunochemical and biochemical properties, whose normal tissue origin is unknown. The distinction between the case of expression of placental-type alkaline phosphatase in human tumors and the expression of a distinct locus in human tumors may provide new information about tumor-specific developmental changes. Antibodies specific for human placental phosphatase and labeled with I-125 have been found to specifically localize in nude mouse xenografts of human tumors that contain the placental-type enzyme. The potential of using specific antibody to human placental phosphatase for diagnosis and/or treatment is also being explored. Complementing the immunochemical studies on this enzyme, peptide mapping and sequenation of relevant peptides is currently being carried out to identify variant-specific substitutions, in the hope of understanding the structural basis for the variation which has been hitherto observed. A new technique for peptide mapping using iodoacetamidofluorescein-labeled cysteinal peptides and specific digestion of the enzyme using highly specific proteases, such as trypsin, has been developed to improve the isolation of appropriate peptides from placental-type phosphatase. The eventual objective of the structural studies is determination of the complete sequence of the enzyme, as well as the substitutions which have occurred in distinct allelic variants and in the cancer-associated enzymes.